Eosinophilia, meningitis and pulmonary nodules in a young woman =============================================================== * Paul E Pfeffer * Arjune Sen * Satya Das * Michael Sheaff * Anand Sivaramakrishnan * David E Simcock * Benjamin Turner * Bronchoscopy * cryptococcus * eosinophilia * imaging/CT MRI etc * multiple pulmonary nodules * opportunist lung infections * respiratory infection A 22-year-old woman was admitted unwell with headache, fever and encephalopathy. She was born in the UK to parents from Hong Kong. She had a past history of asthma, perennial rhinitis and atopic dermatitis for which she took a budesonide 100 μg turbohaler and beclomethasone nasal spray. Three weeks before admission she had returned from holiday in Valencia and shortly after her return developed a flu-like illness followed by worsening asthma symptoms. Despite increasing usage of her corticosteroid turbohaler to eight puffs a day, her cough and wheeze worsened. Her GP prescribed a 5-day course of prednisolone 50 mg daily (approximately 1 mg/kg). Her asthma symptoms improved but she developed a headache 2 days after finishing the corticosteroid course. Over the next 5 days she became more unwell with worsening headache and presented to hospital. On admission she was drowsy with signs of meningism. MRI brain showed a few small hyperintense foci bilaterally. Blood tests showed an eosinophil count of 16.8×109/l (total white cell count 24.4×109/l) and IgE level of 5553 kU/l. Lumbar puncture opening pressure was over 40 cm of water. Cerebrospinal fluid (CSF) white cell count was 33/mm3, with numerous lymphocytes and eosinophils. Serology for HIV-1 and 2 antibodies was negative and HIV RNA was undetectable. Testing for anti-neutrophil cytoplasmic antibodies and anti-nuclear antibodies was negative. A whole body CT scan showed multiple, small, randomly distributed pulmonary nodules (figure 1) and small volume lymphadenopathy in the chest. ![Figure 1](http://thorax.bmj.com/https://thorax.bmj.com/content/thoraxjnl/65/12/1066/F1.medium.gif) [Figure 1](http://thorax.bmj.com/content/65/12/1066/F1) Figure 1 Cross-section (1.5 mm) CT chest images showing pulmonary nodules. ## Questions What is the differential diagnosis of the nodular lesions on CT? What is the next investigation? *See page 1085 for answers* ## Answers *From the questions on page 1066* India ink staining of CSF demonstrated cryptococcus and she was started on flucytosine and amphotericin. *Cryptococcus neoformans* was cultured from the blood (figure 2) and CSF. The differential diagnosis for the pulmonary nodules includes pulmonary cryptococcus, sarcoidosis, disseminated tuberculosis and Wegener's granulomatosis. Sarcoidosis, a common cause of nodular pulmonary shadowing and lymphadenopathy, has an association with cryptococcus.1 This association is due to impaired T-cell function and pulmonary T-cell sequestration in sarcoidosis. In immunocompetent patients pulmonary cryptococcus usually presents on CT as multiple nodules of variable size, although it can present as a solitary nodule and rarely cavitating nodules.2 3 Lymphadenopathy is less common and eosinophilia is recognised.4 ![Figure 2](http://thorax.bmj.com/https://thorax.bmj.com/content/thoraxjnl/65/12/1066/F2.medium.gif) [Figure 2](http://thorax.bmj.com/content/65/12/1066/F2) Figure 2 India ink preparation (×400 magnification) showing numerous capsulated yeasts, typical of *Cryptococcus neoformans*. The next investigation is bronchoscopy with washings, endobronchial and transbronchial biopsy. Transbronchial lung biopsy demonstrated granulomata with cryptococci (figure 3)—the final diagnosis is disseminated cryptococcosis with pulmonary nodules and meningitis. ![Figure 3](http://thorax.bmj.com/https://thorax.bmj.com/content/thoraxjnl/65/12/1066/F3.medium.gif) [Figure 3](http://thorax.bmj.com/content/65/12/1066/F3) Figure 3 Transbronchial lung biopsy with periodic acid Schiff stain (×400 magnification) showing round cryptococcus within lung parenchyma and adjacent granuloma. She required repeat lumbar punctures to reduce CSF pressure. After 1 month of treatment for cryptococcosis her IgE level halved to 2817 kU/l, eosinophilia decreased and headaches abated. Her antifungal treatment was changed to fluconazole. A repeat CT scan showed resolution of the multiple pulmonary nodules and decreased volume of lymphadenopathy. Three months later her IgE level was 1040 kU/l and eosinophilia resolved. No cause of immunodeficiency was found on extensive investigation including T-cell subset analysis and dynamic T-cell function tests. The serum IgE was markedly elevated. Atopic status, with associated T-helper type 2 dominant immune responses, may predispose to invasive fungal infection.5 It is likely that the patient was colonised by cryptococcus with subsequent dissemination after high-dose steroid immunosuppression. Pulmonary cryptococcal infection may increase allergic inflammation and airway responsiveness.6 Cryptococcus is a yeast found worldwide, particularly in soil and bird excrement. It is increasingly recognised to be a cause of disease in immunocompetent as well as immunodeficient individuals. There is a spectrum of cryptococcal lung disease, which may well be underdiagnosed. ## Footnotes * Competing interests None. * Patient consent Obtained. * Provenance and peer review Not commissioned; externally peer reviewed. ## References 1. 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